The project studies are designed to delineate the factors operative in the action of GnRH on pituitary cells and to establish the mechanisms whereby gonadotrope responsiveness can be altered. The overall effects of GnRH on cyclic AMP accumulation, and LH and FSH release, will be assessed using isolated cultured rat pituitary cells. Further studies are aimed at determining the role of events occurring at the plasma membrane, in governing gonadotrope responses to the releasing hormone. This will involve the use of isolated cells and purified plasma membranes, for investigation of hormone-membrane receptor binding, adenylate cyclase activation, GnRH degradation, and localization of GnRH on pituitary cells. Subsequently, studies will determine the effects of changing gonadal steroid concentrations, both in vivo and in vitro, on the various stages of GnRH action at the plasma membrane, in an effort to establish the manner by which steroid hormones exert control over pituitary secretion of gonadotropins.